常咯啉在实验性心律失常狗的药代动力学－药效动力学分析

用Ｈａｒｒｉｓ冠脉结扎法诱发的心律失常狗研究常咯啉药代动力学－药效动力学。７只狗按８３．３３μｇ·ｋｇ￣（－１）·ｍｉｎ￣（－１）静脉滴注６０ｍｉｎ，在给药期间和停药后不同时间记录ＥＣＧ及测定血药浓度。Ｃ－Ｔ数据用药代程序计算药代参数；药效数据用药代－药效同步分析模型计算药效动力学参数，Ｋ１０，Ｔ１／２，Ｖｄ，Ｃｌ分别为０．００８７ｍｉｎ￣（－１），７８．０３ｍｉｎ，４０．５５ｍｌ·ｋｇ￣（－１）和０．４２１ｍｌ·ｋｇ￣（－１）·ｍｉｎ￣（－１）；Ｋｅ０和Ｃｅ（５０）分别为０．００４８ｍｉｎ￣（－１）和２．０１μｇ·ｍｌ￣（－１）.     

Immunotherapy targeting colon cancer stem cells

In the last 10 years, cancer stem cells have interested the scientific community because this small tumorigenic population is also associated with tumor progression in human patients and specific targeting of cancer stem cells could be a strategy to eradicate cancers currently resistant to conventional therapy. Clinical studies have recently demonstrated that adding immune therapy to chemotherapy has survival benefits in comparison with chemotherapy alone that can sensitize tumors to immune cell-mediated killing (e.g., increasing sensitivity of tumor cells to subsequent cytotoxicity by T cells via upregulation of death receptors DR5 and Fas). However, loss of MHC molecules is often observed in cancer cells, rendering tumor cells resistant to CD8 T-cell-mediated cytotoxicity. For this reason, we review the role of other T-cell subsets, such as γδ T and NK cells that are able to efficiently recognize and kill tumor cells and that could be used in passive or active immunotherapy in cancer stem cell eradication.     

New Technique for Endoscopic Removal of Intragastric Balloon Placed for Treatment of Morbid Obesity

Background Placement and removal of the intragastric balloon for obesity are performed endoscopically often under general anesthesia. We propose a safer and faster technique for endoscopic removal of the intragastric balloon using standard sedation. Methods In 87 obese patients, we performed 3 removal techniques: 1) standard gastroscope and foreign body forceps, 2) standard gastroscope and retrieval snare, 3) double-channel gastroscope and foreign body forceps plus symmetrical “shark model” polypectomy snare. Balloon retrieval time, number of times the grasping devices lost the balloon, amount of antispasmodic drug, symptoms cumulative score and VAS score for discomfort were evaluated. Results The technique by double-channel gastroscope and foreign body forceps plus symmetrical polypectomy shark retrieval snare showed a significantly lower balloon retrieval time, number of lost balloons, total number of ampoules used, symptoms cumulative score and VAS score compared to the other two techniques (Dunn’s P < 0.05). Number of lost balloons was positively associated with number of antispasmodic ampoules used, balloon retrieval time and VAS score. Conclusions Technique by double-channel gastroscope and foreign body forceps plus symmetrical polypectomy shark retrieval snare, allows balloon removal safely, quickly and easily, avoiding loss of the balloon, with good patient endurance.     

New susceptibility locus for hypertension on chromosome 8q by efficient pedigree-breaking in an Italian isolate

Essential hypertension (EH) affects a large proportion of the adult population in Western countries and is a major risk factor for cardiovascular diseases. EH is a multifactorial disease with a complex genetic component. To tackle the complexity of this genetic component, we have initiated a study of Campora, an isolated village in South Italy. A random sample of 389 adults was genotyped for a very dense microsatellite genome scan and phenotyped for EH. Of this sample, 173 affected individuals were all related through a 2,180-member pedigree and could be integrated within a linkage analysis. The complexity of the pedigree prevented its direct use for a non-parametric linkage (NPL) analysis. Therefore, the method proposed by Falchi et al. [2004, Am. J. Hum. Genet., 75, 1015-1031] was used for automatic pedigree-breaking. We identified a new locus for EH on chromosome 8q22-23 and detected linkage with two known loci for EH: 1q42-43 and 4p16. Simulations showed that the linkage with 8q22-23 is highly genome-wide significant, even when accounting for the breaking of the pedigree. An extension to qualitative traits of another pedigree-breaking approach [Pankratz et al., 2001, Genet. Epidemiol., 21 (Suppl. 1), S258-S263] also detected a significant linkage on 8q22-23 using a remarkably different set of sub-pedigrees and helped to refine the location of the linkage signal. This work both identifies a new locus strongly linked to hypertension and shows that the power of linkage analysis can be improved by the appropriate use of efficient pedigree-breaking strategies.     

A Peptide from Kiwifruit Exerts Anti-Inflammatory Effects in Celiac Disease Mucosa

Objective: Celiac disease is an immune-mediated disease of the intestine triggered by gluten. Gluten elicits, in genetically susceptible individuals, cytokine responses that are then transmitted to the immunocompetent cells. Vegetables and fruit have anti-inflammatory and antioxidant properties with a protective effect on intestinal epithelium. Kiwifruit is known to have beneficial effects on the intestinal tissues, and it is the only plant food containing the peptide kissper, with anti-inflammatory properties. The aim of this study was the evaluation of the kissper effect on the gluten-induced inflammation in celiac disease.

Methods: We used an in vitro model of intestinal culture explant from celiac disease patients and non-celiac disease patients, cultured for 24 hours with the toxic gliadin peptide P31-43 and kissper preincubation.

Results: Our data showed HLA-DR and TG2 reduction in the celiac disease mucosa pretreated with kissper, as well as a reduction of COX-2 in two patients. No differences we observed for the TGF-b1 and IL-15 levels in supernatants upon kissper pretreatment.

Conclusions: The preliminary results suggest that kissper has a potential anti-inflammatory role in celiac disease.     

Left anterior small thoracotomy (LAST): mid-term results in single vessel disease

BACKGROUND: Left anterior descending artery grafting using the left internal mammary artery via a left anterior small thoracotomy (LAST) gained new popularity in 1994. We review our experience in 250 of 512 patients who underwent a LAST in single vessel left anterior descending artery disease from November 1994 to October 1997. METHODS: Left anterior descending artery stabilization was obtained pharmacologically and mechanically. Two patients (0.8%) had percutaneous transluminal coronary angioplasty at a mean of 23 +/- 5 days; 172 (68.8%) patients had early postoperative angiography. RESULTS: Eight conduits were occluded (patency rate 95.3%). There was only one late death. Cumulative angiography and Doppler flow evaluation showed that 96.8% of the anastomoses were patent and 95.6% were both patent and nonrestrictive. At a mean follow-up of 16.3 +/- 9.3 months, 9 (3.6%) patients had redo-surgery due to anastomotic/conduit failure and 249 (99.6%) patients were alive and asymptomatic. No patients had acute myocardial infarction. The 35-month actuarial survival rate was 99.6% +/- 0.4%, and the event-free survival rate for the entire experience was 93.7% +/- 1.3%. If only the last 157 patients are considered, at 18 months event-free survival was higher than in the entire group of patients (96.4% +/- 1.4% vs 93.7% +/- 1.3%, p = 0.05). CONCLUSIONS: New instrumentation has made the operation easier and has contributed to its spread, along with increased experience and the end of the learning curve. At the moment we consider the LAST a more anatomical and physiological surgical approach to single vessel coronary disease.     

BMP2,3,4,5 mRNA在三叉神经中的表达分析

目的：明确 Ｂ Ｍ Ｐｓ 与外周神经的关系。方法：用原位杂交方法观察 Ｂ Ｍ Ｐ２,３,４,５ 的ｍ Ｒ Ｎ Ａ在三叉神经中的表达。结果：在外周神经（三叉神经）中均有 Ｂ Ｍ Ｐ２,３,４,５ ｍ Ｒ Ｎ Ａ 分布, Ｂ Ｍ Ｐ２,３,４,５ 的分布主要位于构成神经纤维髓鞘的雪旺细胞中;此外发现 Ｂ Ｍ Ｐ２ 在部分神经纤维中也有表达。结论：首次确定了 Ｂ Ｍ Ｐ２,３,４,５ 在外周神经中的表达和分布,揭示了 Ｂ Ｍ Ｐ２,３,４,５可能在外周神经的发育和再生以及形态结构的维持中发挥着调控作用。